title: Identification of a novel cyclin required for the intrinsic apoptosis pathway in lymphoid cells.
abstract: We have identified an early step common to pathways activated by different forms of intrinsic apoptosis stimuli. It requires de novo synthesis of a novel cyclin, cyclin O, that forms active complexes primarily with Cdk2 upon apoptosis induction in lymphoid cells. Cyclin O expression precedes glucocorticoid and gamma-radiation-induced apoptosis in vivo in mouse thymus and spleen, and its overexpression induces caspase-dependent apoptosis in cultured cells. Knocking down the endogenous expression of cyclin O by shRNA leads to the inhibition of glucocorticoid and DNA damage-induced apoptosis due to a failure in the activation of apical caspases while leaving CD95 death receptor-mediated apoptosis intact. Our data demonstrate that apoptosis induction in lymphoid cells is one of the physiological roles of cyclin O and it does not act by perturbing a normal cellular process such as the cell cycle, the DNA damage checkpoints or transcriptional response to glucocorticoids.
authors.affiliation: Apoptosis Signalling Group, Cancer Research Programme, Institut Municipal d'Investigació Mèdica, Parc de Recerca Biomèdica de Barcelona, Dr. Aiguader, 88. 08003 Barcelona, Spain.
authors.forename: M B
authors.initials: MB
authors.lastname: Roig
authors.forename: R
authors.initials: R
authors.lastname: Roset
authors.forename: L
authors.initials: L
authors.lastname: Ortet
authors.forename: N A
authors.initials: NA
authors.lastname: Balsiger
authors.forename: A
authors.initials: A
authors.lastname: Anfosso
authors.forename: L
authors.initials: L
authors.lastname: Cabellos
authors.forename: M
authors.initials: M
authors.lastname: Garrido
authors.forename: F
authors.initials: F
authors.lastname: Alameda
authors.forename: H J M
authors.initials: HJ
authors.lastname: Brady
authors.forename: G
authors.initials: G
authors.lastname: Gil-Gómez
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D045647:DNA Glycosylases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D016213:Cyclins; D005938:Glucocorticoids; C539096:cyclin O, mouse; D051357:Cyclin-Dependent Kinase 2; C492570:CCNO protein, human; D045647:DNA Glycosylases; D053148:Caspase 3; D020169:Caspases